ABSTRACT
OBJECTIVE To explore the risk signals of Fluocinolone acetonide intravitreal implants and promote safe and rational drug use for patients. METHODS Based on the data from the Hainan Province Franchised Drug Adverse Reaction Monitoring Subsystem (hereinafter referred to as the “Franchised Drug Monitoring System”) and the FDA Adverse Event Reporting System (FAERS), the adverse drug reaction (ADR)/adverse drug event (ADE) reports of Fluocinolone acetonide intravitreal implants were coded by using system organ classification and preferred terminology, and relevant patient information was collected. Risk signal mining was carried out by using the reporting odds ratio (ROR) method and the comprehensive standards method of the UK Medicines and Healthcare Products Regulatory Agency (hereinafter referred to as the “MHRA method”). RESULTS Among the 72 reports of Fluocinolone acetonide intravitreal implants received by the Franchised Drug Monitoring System, the ratio of male to female was 1∶1.4, the patient’s age was mainly distributed between 18 and 64 years old; ADR/ADE affected 5 systemic organs, with eye organ diseases accounting for 87.7%; among them, there were 9 new and general ADR reports (12.5%) and 4 severe ADR reports (5.6%); ROR method and MHRA method both identified three risk signals: cataracts, glaucoma, and high intraocular pressure. Among the 244 reports received by the FAERS database, the ratio of male to female was 1∶1.5; ADR/ADE damage affected 10 systemic organs, with 46.1% suffering from various injuries, poisoning, and operational complications, and 32.0% suffering from product problems; there were 20 severe ADR reports (8.2%); ROR method and MHRA method both identified 19 risk signals, including implantation complications, medication system issues, etc. CONCLUSIONS When using Fluocinolone acetonide intravitreal implants in clinical practice, in addition to paying attention to eye ADR/ADE such as high intraocular pressure, cataracts, and glaucoma, attention should also be paid to the potential risks caused by ADE due to product quality and unreasonable use.
ABSTRACT
Background@#and Purpose Migraine is a condition that is often observed to run in families, but its complex genetic background remains unclear. This study aimed to identify the genetic factors influencing migraines and their potential association with the family medical history. @*Methods@#We performed a comprehensive genome-wide association study of a cohort of 1,561 outpatients with migraine and 473 individuals without migraine in Taiwan, including Han Chinese individuals with or without a family history of migraine. By analyzing the detailed headache history of the patients and their relatives we aimed to isolate potential genetic markers associated with migraine while considering factors such as sex, episodic vs. chronic migraine, and the presence of aura. @*Results@#We revealed novel genetic risk loci, including rs2287637 in DEAD-Box helicase 1 and long intergenic non-protein coding RNA 1804 and rs12055943 in engulfment and cell motility 1, that were correlated with the family history of migraine. We also found a genetic location downstream of mesoderm posterior BHLH transcription factor 2 associated with episodic migraine, whereas loci within the ubiquitin-specific peptidase 26 exonic region, dual specificity phosphatase 9 and pregnancy-upregulated non-ubiquitous CaM kinase intergenic regions, and poly (ADP-ribose) polymerase 1 and STUM were linked to chronic migraine. We additionally identified genetic regionsassociated with the presence or absence of aura. A locus between LINC02561 and urocortin 3 was predominantly observed in female patients. Moreover, three different single-nucleotide polymorphisms were associated with the family history of migraine in the control group. @*Conclusions@#This study has identified new genetic locations associated with migraine and its family history in a Han Chinese population, reinforcing the genetic background of migraine. The findings point to potential candidate genes that should be investigated further.
ABSTRACT
ObjectiveTo investigate the epidemic characteristics and influencing factors of acute conjunctivitis caused by human adenovirus(HAdv)in Yantian District of Shenzhen City, Guangdong Province from 2014 to 2022, and to provide evidence for formulating effective prevention and control measures. MethodsDescriptive epidemiology was used to analyze the epidemiological characteristics of acute hemorrhagic conjunctivitis (AHC) cases reported from the Chinese disease prevention and control information system. Etiological characteristics of laboratory-confirmed cases were analyzed, and a case-control study method of test-negative design (TND) was conducted as well. According to the result of HAdv detection, analysis was used to identify the influencing factors of morbidity. ResultsA total of 1 005 AHC cases were reported in Yantian District, Shenzhen City from 2014 to 2022, with an average annual incidence rate of 49.49/105. The incidence rate ranged from 4.67/105 to 117.28/105. The peak incidence occurred from July to October each year, with a male-to-female ratio of 1.42∶1. The median (P25,P75) age of onset was 29(12,40) years. A total of 716 eye swabs were collected for etiological detection from 2014 to 2022. HAdv positive detection rate was 36.45% (263/716), Cox 24v positive detection rate was 0.28% (2/716), while EV70 was not detected. The longest viral shedding time in eye swabs was 10 days, with a median of 2 days. The highest HAdv positive detection rate (47.47%) was observed when the sampling-to-onset interval was 4‒5 days, and the difference was statistically significant (P<0.05), with a trend of first increasing and then decreasing. Multivariate logistic regressing analysis showed that aged 18‒ years, and average temperature higher than 24.90 ℃ 3 days before onset (P<0.05) were the risk factors for acute HAdv conjunctivitis. ConclusionAHC in Yantian District, Shenzhen City showed a low level of prevalence from 2014 to 2022, with HAdv being the predominant pathogen. The peak period of viral shedding occurred on the 4th to 5th day after symptom onset, suggesting the importance of adherence to strict home isolation for infected persons. Aged18‒ years and average temperature increased 3 days before onset are associated with an increased risk of adenoviral conjunctivitis. It is recommended to strengthen personal protection and keep doing a good job of AHC surveillance and early warning, so as to timely prevent the outbreaks of AHC.
ABSTRACT
OBJECTIVE@#To investigate the in vivo intervention and relative mechanism of Genistein (GEN) on tumor-associated inflammatory and tumor thrombophilia in lymphoma-bearing mice.@*METHODS@#Forty female Balb/c mice aged 5-6 weeks were injected with murine-derived Pro B-cell lymphoma cell line 38B9 to establish a lymphoma mouse model, which was randomly divided into control group, tumor-bearing group, GEN drug intervention group and cyclophosphamide (CTX)drug intervention group. Histopathologic was used to evaluate the tumorigenesis. Tumor formation was observed, and tumor tissues were collected of HE and immunohistochemical staining. ELISA and flow cytometry were used to detect the expression of inflammatory factors and the changes of thrombus indices in plasma after intervention of GEN and Cyclophosphamide (CTX) respectively. Immunohistochemistry method was used to detect the expression of CD19 in tomor tissues of tummor bearing mice.@*RESULTS@#After 14 days of tumor bearing, the mice were tumorigenic. The lymphoma cells were diffusely distributed in the tumor tissue and the expression of CD19 in the tumor tissue was positive. The inflammatory factors such as IL-6, NETs and CLEC-2, and thrombotic indices such as TF, FIB and D-D in lymphoma-bearing mice were significantly higher than those before tumor-injection and lower than those after drug-intervention (all P<0.05). The levels of CLEC-2 and D-D in GEN group were significantly lower than those in CTX group (P<0.05).@*CONCLUSION@#Tumor-associated inflammation and thrombophilia exist in lymphoma-bearing mice. GEN shows better anti-inflammatory and anti-thrombotic effects compared with CTX by interfering with tumor inflammatory factors.
Subject(s)
Mice , Female , Animals , Genistein , Lymphoma , Cyclophosphamide , Thrombophilia , Inflammation , Lectins, C-TypeABSTRACT
OBJECTIVE@#To investigate the efficacy and safety of daratumumab in treatment of multiple myeloma (MM) patients with renal impairment (RI).@*METHODS@#The clinical data of 15 MM patients with RI who received daratumumab-based regimen from January 2021 to March 2022 in three centers were retrospectively analyzed. Patients were treated with daratumumab or daratumumab combined with dexamethasone or daratumumab combined with bortezomib and dexamethasone and the curative effect and survival were analyzed.@*RESULTS@#The median age of 15 patients was 64 (ranged 54-82) years old. Six patients were IgG-MM, 2 were IgA-MM,1 was IgD-MM and 6 were light chain MM. Median estinated glomerular filtration rate (eGFR) was 22.48 ml/(min·1.73 M2). Overall response rate of 11 patients with MM was 91% (≥MR), including 1 case of stringent complete response (sCR), 2 cases of very good partial response (VGPR), 3 cases of partial response (PR) and 4 cases of minor response (MR). The rate of renal response was 60%(9/15), including 4 cases of complete response (CR), 1 case of PR and 4 cases of MR. A median time of optimal renal response was 21 (ranged 7-56) days. With a median follow-up of 3 months, the median progression-free survival and overall survival of all patients were not reached. After treatment with daratumumab-based regimen, grade 1-2 neutropenia was the most common hematological adverse reaction. Non-hematological adverse reactions were mainly infusion-related adverse reactions and infections.@*CONCLUSION@#Daratumumab-based regimens have good short-term efficacy and safety in the treatment of multiple myeloma patients with renal impairment.
Subject(s)
Humans , Middle Aged , Aged , Aged, 80 and over , Multiple Myeloma/drug therapy , Retrospective Studies , Dexamethasone/therapeutic use , Antibodies, Monoclonal/therapeutic use , Bortezomib/therapeutic use , Renal Insufficiency/drug therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic useABSTRACT
The leaves of sea buckthorn(Hippophae rhamnoides), considered as common food raw materials, have records of medicinal use and diverse pharmacological activities, showing a potential medicinal value. However, the active substances in the sea buckthorn leaves and their mechanisms of action remain unclear. In addition, due to the extensive source and large variety variations, the quality evaluation criteria of sea buckthorn leaves remain to be developed. To solve the problems, this study predicted the main active components, core targets, key pathways, and potential pharmacological effects of sea buckthorn leaves by network pharmacology and molecular docking. Furthermore, ultra-performance liquid chromatography with diode-array detection(UPLC-DAD) was employed to determine the content of active components and establish the chemical fingerprint, on the basis of which the quality markers of sea buckthorn leaves were predicted and then verified by the enzyme activity inhibition method. The results indicated that sea buckthorn leaves had potential therapeutic effects on a variety of digestive tract diseases, metabolic diseases, tumors, and autoimmune diseases, which were consistent with the ancient records and the results of modern pharmacological studies. The core targets of sea buckthorn leaves included PTPN11, AKT1, PIK3R1, ESR1, and SRC, which were mainly involved in the PI3K-AKT, MAPK, and HIF-1 signaling pathways. In conclusion, the active components of sea buckthorn leaves are associated with the rich flavonoids and tannins, among which quercitrin, narcissoside, and ellagic acid can be used as the quality markers of sea buckthorn leaves. The findings provide a reference for the quality control and further development and utilization of sea buckthorn leaves as medicinal materials.
Subject(s)
Hippophae/chemistry , Network Pharmacology , Molecular Docking Simulation , Phosphatidylinositol 3-Kinases/metabolism , Flavonoids/analysis , Fruit/chemistryABSTRACT
Objective: To investigate the association between gestational diabetes mellitus (GDM) and preterm birth subtypes. Methods: Based on the cohort of pregnant women in Anqing Prefectural Hospital, the pregnant women who received prenatal screening in the first or second trimesters were recruited into baseline cohorts; and followed up for them was conducted until delivery, and the information about their pregnancy status and outcomes were obtained through electronic medical record system and questionnaire surveys. The log-binomial regression model was used to explore the association between GDM and preterm birth [iatrogenic preterm birth, spontaneous preterm birth (preterm premature rupture of membranes and preterm labor)]. For multiple confounding factors, the propensity score correction model was used to compute the adjusted association. Results: Among the 2 031 pregnant women with a singleton delivery, the incidence of GDM and preterm birth were 10.0% (204 cases) and 4.4% (90 cases) respectively. The proportions of iatrogenic preterm birth and spontaneous preterm birth in the GDM group (n=204) were 1.5% and 5.9% respectively, while the proportions in non-GDM group (n=1 827) were 0.9% and 3.2% respectively, and the difference in the proportion of spontaneous preterm birth between the two groups was significant (P=0.048). Subtypes of spontaneous preterm were further analyzed, and the results showed that the proportions of preterm premature rupture of membranes and preterm labor in the GDM group were 4.9% and 1.0% respectively, while the proportions in the non-GDM group were 2.1% and 1.1% respectively. It showed that the risk of preterm premature rupture of membranes in GDM pregnant women was 2.34 times (aRR=2.34, 95%CI: 1.16-4.69) higher than that in non-GDM pregnant women. Conclusions: Our results showed that GDM might increase the risk of preterm premature rupture of membranes. No significant increase in the proportion of preterm labor in pregnant women with GDM was found.
Subject(s)
Infant, Newborn , Female , Pregnancy , Humans , Premature Birth , Diabetes, Gestational , Obstetric Labor, Premature , Hospitals , Iatrogenic DiseaseABSTRACT
Periodontitis can lead to periodontal tissue defect, tooth mobility and loss, which seriously affects the quality of life. Periodontal regeneration surgery is an important treatment method for repairing periodontal defects, and it is also the hotspot of current periodontal clinical and basic research. A comprehensive understanding of the factors affecting the efficacy of periodontal regenerative surgery can improve clinicians' periodontal treatment concepts, increases the predictability of treatment results, and enhances the level of clinical diagnosis and periodontal treatment. In order to instruct the clinicians, this article will explain the basic principles of periodontal regeneration and the key points of periodontal wound healing, and analyze the elements of periodontal regeneration surgery, which including the patient-related factors, local factors, surgical factors and regenerative material selection.
ABSTRACT
Enamel matrix proteins (EMP) are deposited on the surface of developing roots before dentin formation and may play a role in osteogenesis. Amelogenins (Am) are the main and active component in EMPs. Studies had showed great clinical values of EMPs in periodontal regenerative treatment and other fields. By affecting the expression of growth factors and inflammatory factors, EMPs could act on various periodontal regeneration-related cells to promote angiogenesis, anti-inflammation, bacteriostasis and tissue healing, achieving the clinical effect of periodontal tissue regeneration (newly generated cements and alveolar bones as well as functionally penetrated periodontal ligament). EMPs alone or combined with bone graft material and barrier can be used for regenerative surgical treatment in intrabony defects and degree Ⅱ furcation-involved at maxillary buccal or mandibular teeth. EMPs can also be adjunctively used to treat recession type 1 or 2 gingival recessions, forming periodontal regeneration on the exposed root surface. Through a comprehensive understanding of the principle and current clinical application of EMPs on periodontal regeneration, we can look forward to their future development. The development of recombinant human amelogenin to replace animal-derived EMPs through bioengineering technologies, the study of the clinical application of EMPs combined with other collagen biomaterials, and the specific application of EMPs in severe soft and hard periodontal tissue defects and peri-implant lesions are all important development directions of future EMPs-related researches.
ABSTRACT
OBJECTIVE@#To construct a myeloproliferative neoplasms (MPN) transplanted mouse model with JAK2-V617F, MPLW515L or CALR-Type I gene mutation, and establish a systematic evaluation system to verify the success of model construction.@*METHODS@#The bone marrow c-kit+ cells of the mice were obtained by the following steps: The mice were killed by cervical dislocation, the femur, tibia and ilium were separated, and the bone marrow cells were collected. The c-kit+ cells were sorted after incubation with CD117 magnetic beads. The method of constructing mouse primary mutant cells is as follows: A gene mutation vector with a GFP tag was constructed by the retroviral system, and the retroviral vector was packaged into the Platinum-E cells to obtain the virus supernatant, and then used it to infect the c-kit+ cells of mice. The MPN mouse model was constructed as follows: the mouse primary c-kit+ cells containing the mutant genes were collected after infection, and then transplanted them via the tail vein into the female recipient mice of the same species which were irradiated with a lethal dose of gamma rays (8.0 Gy). The MPN mouse model was evaluated as follows: After transplantation, the peripheral blood of the mice was regularly collected from the tail vein to perform the complete blood count test, and the size of spleen and the degree of bone marrow fibrosis were estimated.@*RESULTS@#The mouse c-kit+ cells with the mutant genes were successfully obtained from the bone marrow. MPN mouse model was successfully constructed: The peripheral blood cells of the MPN-transplanted mice carried exogenous implanted GFP-positive cells, and the white blood cells (WBC), platelet (PLT) and hematocrit (HCT) were all increased; the body weight loss, and the water and food intake were reduced in the transplanted mice; further pathological analysis showed that the transplanted mice displayed splenomegaly and bone marrow fibrosis. These results suggested that the MPN mouse model was successfully constructed. According to the common and different characteristics of the three MPN mouse model, a preliminary evaluation system for judging the success of MPN mouse model construction was summarized, which mainly included the following indicators, for example, the proportion of GFP-positive cells in the peripheral blood of mice; WBC, PLT and HCT; the degree of spleen enlargement and the bone marrow fibrosis.@*CONCLUSION@#The MPN mouse model with JAK2-V617F, MPLW515L or CALR-Type I gene mutation is successfully established by retroviral system, which can provide an important experimental animal model for the research of MPN pathogenesis and drug-targeted therapy.
Subject(s)
Female , Mice , Animals , Primary Myelofibrosis , Myeloproliferative Disorders/genetics , Bone Marrow/pathology , Mutation , Disease Models, Animal , Neoplasms , Janus Kinase 2/geneticsABSTRACT
OBJECTIVE@#To investigate the safety and efficacy of novel CD19-KIRS2/Dap12-BB chimeric antigen receptor T cells (CAR-T cells) in the treatment of relapsed/refractory B-cell malignancy (R/R BCM).@*METHODS@#Three patients with R/R BCM treated with novel CD19-KIRS2/Dap12-BB CAR-T cells from June 2020 to November 2020 were enrolled, including 1 case of B-cell acute lymphoblastic leukaemia (B-ALL) and 2 cases of non-Hodgkin's lymphoma (NHL), and the efficacy and adverse reactions were observed.@*RESULTS@#After CAR-T cells infusion, patient with B-ALL achieved complete remission (CR) and minimal residual disease (MRD) turned negative, and 2 patients with NHL achieved partial remission (PR). Grade 2 cytokine release syndrome (CRS) occurred in B-ALL patient, grade 1 CRS occurred in 2 NHL patients, and grade II to IV hematologic adverse reactions occurred in 3 patients, all of which were controllable and reversible. The progression-free survival (PFS) of the 3 patients was 143, 199, and 91 days, and overall survival (OS) was 282, 430, and 338 days, respectively.@*CONCLUSION@#The novel CD19-KIRS2/Dap12-BB CAR-T cells in treatment of 3 patients with R/R BCM have significant short-term efficacy and controllable adverse reactions, but the long-term efficacy needs to be further improved.
Subject(s)
Humans , Receptors, Chimeric Antigen , Immunotherapy, Adoptive , Burkitt Lymphoma , Antigens, CD19 , Neoplasm, Residual , Adaptor Proteins, Signal TransducingABSTRACT
OBJECTIVE@#To monitor the changes of voriconazole minimum concentration(Cmin) in patients with hematological diseases, and evaluate the factors influencing and adverse reactions of voriconazole clearance in patients with hematological diseases, so as to provide a theoretical basis for reasonable clinical use of voriconazole.@*METHODS@#136 patients with hematological diseases who used voriconazole in Wuhan NO.1 Hospital from May 2018 to December 2019 were selected. The correlation between C-reactive protein, albumin, creatinine and voriconazole Cmin were analyzed, and the changes of voriconazole Cmin after glucocorticoid treatment was also detected. In addition, stratified analysis was used to explore the adverse events of voriconazole.@*RESULTS@#Among 136 patients, 77 were male (56.62%) and 59 were female (43.38%). There were positive correlations between voriconazole Cmin and C-reactive protein and creatinine levels (r=0.277, r=0.208), while voriconazole Cmin was negatively correlated with albumin level (r=-2.673). Voriconazole Cmin in patients treated with glucocorticoid was decreased significantly (P<0.05). In addition, sratified analysis of voriconazole Cmin showed that compared with voriconazole Cmin 1.0-5.0 mg/L group, the incidence of adverse reactions of visual impairment in voriconazole Cmin> 5.0 mg/L group was increased (χ2=4.318, P=0.038).@*CONCLUSION@#The levels of C-reactive protein, albumin and creatinine are closely related to the voriconazole Cmin, which indicate that inflammation and hyponutrition may prevent the clearance of voriconazole in patients with hematological diseases. It is necessary to monitor the voriconazole Cmin of patients with hematological diseases, and adjust the dosage in time to reduce adverse reactions.
Subject(s)
Humans , Male , Female , Voriconazole/therapeutic use , Antifungal Agents/therapeutic use , C-Reactive Protein , Creatinine , Glucocorticoids , Retrospective Studies , Drug Monitoring , Hematologic DiseasesABSTRACT
OBJECTIVE@#To investigate the effect of hemoglobin (Hb) on the efficacy of chimeric antigen receptor T cell therapy (CAR-T) in patients with multiple myeloma (MM).@*METHODS@#From June 2017 to December 2020, 76 MM patients who received CAR-T therapy in the Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, with complete clinical data and evaluable efficacy, were selected as the research objects. According to the receiver operating characteristic (ROC) curve, the best cut-off value was obtained. The patients were divided into groups on the basis of Hb 105.5 g/L as the cut-off value. The age, sex, serum calcium, β2-microglobulin, serum creatinine, lactate dehydrogenase (LDH), and the influencing factors of CAR-T treatment efficacy in MM patients were analyzed.@*RESULTS@#Hb was an influencing factor of efficacy. Univariate analysis showed that Hb, LDH, and albumin affected the efficacy of CAR-T therapy. Multivariate analysis showed that Hb ( OR=1.039, 95% CI: 1.002-1.078) and LDH ( OR=1.014, 95% CI: 1.000-1.027) were the influencing factors for the efficacy of CAR-T therapy.@*CONCLUSION@#The efficacy of CAR-T therapy in MM patients with low Hb is poor, and Hb is a factor affecting the efficacy of CAR-T therapy.
Subject(s)
Humans , Multiple Myeloma/drug therapy , Receptors, Chimeric Antigen , Immunotherapy, Adoptive , Treatment Outcome , Hematologic DiseasesABSTRACT
Objective:To investigate risk factors for decompressive craniectomy (DC) after endovascular therapy (EVT) in patients with acute anterior circulation ischemic stroke.Methods:Patients underwent EVT due to acute anterior circulation large vessel occlusion in Liaocheng Brain Hospital from January 2018 to January 2020 were retrospectively included. They were divided into DC group and non-DC group. Univariate and multivariate logistic regression analyses were used to determine risk factors for DC after EVT. Results:A total of 207 patients were enrolled, 126 were male (60.87%), and their age was 66.22±11.24 years old. The baseline National Institutes of Health Stroke Scale (NIHSS) score was 19.84±9.20, and the Alberta Stroke Program Early CT Score (ASPECTS) was 7.98±0.66. The immediate postoperative modified Treatment In Cerebral Ischemia (mTICI) blood flow grade in seven patients (5.80%) was ≤2a, 30 (14.49%) experienced hemorrhagic transformation (HT) after procedure, and 28 (13.5%) received DC. There were statistically significant differences between the DC group and the non-DC group in terms of past stroke history, preoperative NIHSS score and ASPECTS, vascular occlusion site, EVT time, immediate postoperative mTICI ≤2a, and HT (all P<0.05). Multivariate logistic regression analysis showed that atrial fibrillation (odds ratio [ OR] 3.202, 95% confidence interval [ CI] 1.335-9.796; P=0.011), previous stroke history ( OR 2.655, 95% CI 1.016-6.938; P=0.046), high preoperative NIHSS score ( OR 1.074, 95% CI 1.026-1.124; P=0.002), internal carotid artery occlusion ( OR 4.268, 95% CI 1.399-13.024; P=0.011), longer EVT time ( OR 1.010, 95% CI 1.003-1.016; P=0.003), mTICI grade ≤2a ( OR 5.342, 95% CI 1.565-18.227; P=0.007) and postoperative HT ( OR 3.036, 95% CI 1.024-9.004; P=0.045) were independent risk factors for DC. Conclusions:It is not uncommon for patients with acute anterior circulation ischemic stroke to need DC after EVT. Previous stroke history, atrial fibrillation, high baseline NIHSS score, internal carotid artery occlusion, prolonged blood EVT time, mTICI grade ≤2a and postoperative HT are independent predictors of needing DC after EVT.
ABSTRACT
Objective:To investigate the clinical application value and safety of magnetically controlled capsule gastroscopy (MCCG) in gastric and duodenal examination of children in comparison with conventional gastroscopy.Methods:Data of 160 outpatients or inpatients with abdominal pain accompanied by Helicobacter pylori infection aged 8-16 who underwent either MCCG or conventional gastroscopy in Shanghai Children's Hospital from March 2020 to March 2022 were retrospectively analyzed. Children were divided into the MCCG group ( n=80) and the conventional gastroscopy group ( n=80) according to different examination methods. The detection and examination time of lesions in upper gastrointestinal tract, tolerance and safety between the two groups were analyzed. Results:MCCG was successfully performed in 79 children and conventional gastroscopy was successfully performed in 78 children, respectively. The positive detection rates were 1.3% (1/79) and 1.3% (1/78) in the esophagus ( χ2=0.000, P>0.999), 87.3% (69/79) and 91.0% (71/78) in the stomach ( χ2=0.552, P=0.327) , 15.2% (12/79) and 19.2% (15/78) in duodenum ( χ2=0.450, P=0.533) with no significant difference between the two groups. There was no significant difference in the examination time [72.0 (41.0, 109.5) min VS 6.0 (4.3, 7.0) min, U=24, P<0.001] in the MCCG group and the conventional gastroscopy group. No adverse event occurred in either group. Conclusion:There is no significant difference in the detection rate of gastric and duodenal lesions between the MCCG group and the conventional gastroscopy group. MCCG is safe and stable, and can be used as an diagnostic tool for gastric and duodenal diseases in children.
ABSTRACT
Objective: To observe the effect of platelets on hematopoietic stem cell (HSCs) implantation in mice with radiation-induced bone marrow injury and bone marrow transplantation models. Methods: ①Male C57BL/6 mice were divided into a single irradiation group and a radiation infusion group after receiving (60)Co semimyeloablative irradiation for 18-10 weeks. The irradiation infusion group received 1×10(8) platelets expressing GFP fluorescent protein. ② The allogeneic bone marrow transplantation model was established. The experimental groups included the simple transplantation group (BMT) and the transplantation infusion group (BMT+PLT). The BMT group was infused through the tail vein only 5 × 10(6) bone marrow cells, the BMT+PLT group needs to be infused with bone marrow cells at the same time 1× 10(8) platelets. ③ Test indicators included peripheral blood cell and bone marrow cell counts, flow cytometry to detect the proportion of hematopoietic stem cell (HSC) and hematopoietic progenitor cells, bone marrow cell proliferation and apoptosis, and pathological observation of vascular niche damage and repair. Results: ①On the 3rd, 7th, 14(th), and 21st days after irradiation, the bone marrow cell count of the infusion group was higher than that in the single irradiation group (P<0.05), and the peripheral blood cell count was also higher. A statistically significant difference was found between the white blood cell count on the 21st day and the platelet count on the 7th day (P<0.05). In the observation cycle, the percentage of bone marrow cell proliferation in the infusion group was higher, while the percentage of apoptosis was lower. ② The results of bone tissue immunofluorescence after irradiation showed that the continuity of hematopoietic niche with red fluorescence was better in the irradiation infusion group. ③The chimerism percentage in the BMT+PLT group was always higher than that in the BMT group after transplantation.④ The BMT+PLT group had higher bone marrow cell count and percentage of bone marrow cell proliferation on the 7th and 28th day after transplantation than that in the BMT group, and the percentage of bone marrow cell apoptosis on the 14th day was lower than that in the BMT group (P<0.05). After the 14th day, the percentage of stem progenitor cells in the bone marrow cells of mice was higher than that in the BMT group (P<0.05). ⑤The immunohistochemical results of bone marrow tissue showed that the continuity of vascular endothelium in the BMT+PLT group was better than that in the BMT group. Conclusion: Platelet transfusion can alleviate the injury of vascular niche, promotes HSC homing, and is beneficial to hematopoietic reconstruction.
Subject(s)
Mice , Animals , Bone Marrow Transplantation , Bone Marrow , Mice, Inbred C57BL , Hematopoietic Stem Cells , Bone Marrow Diseases , Hematopoietic Stem Cell Transplantation , Mice, Inbred BALB CABSTRACT
Objective: To explore the prognostic factors of extracellular NK/T cell lymphoma (ENKTL) treated with pegaspargase/L-asparaginase. Methods: The clinical data of 656 ENKTL patients diagnosed at 11 medical centers in the Huaihai Lymphoma Working Group from March 2014 to April 2021 were retrospectively analyzed. The patients were randomly divided into two groups: a training set (460 cases) and a validation set (196 cases) at 7∶3, and the prognostic factors of the patients were analyzed. A prognostic scoring system was established, and the predictive performance of different models was compared. Results: Patients' median age was 46 (34, 57) years, with 456 males (69.5% ) and 561 nasal involvement (85.5% ). 203 patients (30.9% ) received a chemotherapy regimen based on L-asparaginase combined with anthracyclines, and the 5-year overall survival rate of patients treated with P-GEMOX regimen (pegaspargase+gemcitabine+oxaliplatin) was better than those treated with SMILE regimen (methotrexate+dexamethasone+cyclophosphamide+L-asparaginase+etoposide) (85.9% vs 63.8% ; P=0.004). The results of multivariate analysis showed that gender, CA stage, the Eastern Cooperative Oncology Group performance status (ECOG PS) score, HGB, and EB virus DNA were independent influencing factors for the prognosis of ENKTL patients (P<0.05). In this study, the predictive performance of the prognostic factors is superior to the international prognostic index, Korean prognostic index, and prognostic index of natural killer lymphoma. Conclusion: Gender, CA stage, ECOG PS score, HGB, and EB virus DNA are prognostic factors for ENKTL patients treated with pegaspargase/L-asparaginase.
Subject(s)
Male , Humans , Middle Aged , Asparaginase/therapeutic use , Prognosis , Retrospective Studies , Lymphoma, Extranodal NK-T-Cell/drug therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Etoposide , Cyclophosphamide , Methotrexate/therapeutic use , DNA/therapeutic use , Treatment OutcomeABSTRACT
Objective: To observe the characteristics of the evolution of liver indexes in patients with relapsed/refractory multiple myeloma (RRMM) treated with CAR-T-cells based on BCMA. Methods: Retrospective analysis was performed of patients with RRMM who received an infusion of anti-BCMA CAR-T-cells and anti-BCMA combined with anti-CD19 CAR-T-cells at our center between June 1, 2019, and February 28, 2023. Clinical data were collected to observe the characteristics of changes in liver indexes such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), and direct bilirubin (DBIL) in patients, and its relationship with cytokine-release syndrome (CRS) . Results: Ninety-two patients were included in the analysis, including 41 patients (44.6%) in the group receiving a single infusion of anti-BCMA CAR-T-cells, and 51 patients (55.4%) in the group receiving an infusion of anti-BCMA combined with anti-CD19 CAR-T-cells. After infusing CAR-T-cells, 31 patients (33.7%) experienced changes in liver indexes at or above grade 2, which included 20 patients (21.7%) with changes in one index, five patients (5.4%) with changes in two indexes, and six patients (6.5%) with changes in three or more indexes. The median time of peak values of ALT and AST were d17 and d14, respectively, and the median duration of exceeding grade 2 was 5.0 and 3.5 days, respectively. The median time of peak values of TBIL and DBIL was on d19 and d21, respectively, and the median duration of exceeding grade 2 was 4.0 days, respectively. The median time of onset of CRS was d8, and the peak time of fever was d9. The ALT, AST, and TBIL of patients with CRS were higher than those of patients without CRS (P=0.011, 0.002, and 0.015, respectively). CRS is an independent factor that affects ALT and TBIL levels (OR=19.668, 95% CI 18.959-20.173, P=0.001). The evolution of liver indexes can be reversed through anti-CRS and liver-protection treatments, and no patient died of liver injury. Conclusions: In BCMA-based CAR-T-cell therapy for RRMM, CRS is an important factor causing the evolution of liver indexes. The evolution of liver indexes after CAR-T-cell infusion is transient and reversible after treatment.
Subject(s)
Humans , Antigens, CD19 , B-Cell Maturation Antigen/therapeutic use , Bilirubin , Immunotherapy, Adoptive , Liver , Multiple Myeloma/drug therapy , Retrospective Studies , T-LymphocytesABSTRACT
Objective To explore the role pathway and pattern of the myeloma cancer gene (MYC) and its mRNA interaction with the microRNAs(miRNAs) and circular RNA(circRNAs) at hour 0, hour 6 and hour 72 in the rat liver regeneration. Methods The rat 2/3 hepatectomy (PH) model was prepared as described by Higgins, the hepatocytes were isolated according to the method of Smedsrod et al. The expression changes of mRNA, miRNA and circRNA [together named as competing endogenous RNA (ceRNA)] were detected by the large-scale quantitative detection technology, the interaction network of ceRNA was constructed by Cytoscape 3.2 software, and their correlation in expression and role were analyzed by ceRNA comprehensive analysis. Results It was found that at hour 0 and hour 6 after PH, the ratio value of MYC mRNA showed 0.15±0.03 and 2.36±0.20, miR-134-5p indicated 3.22±0.61 and 0.08±0.02, circRNA_12112 displayed 0.68±0.21 and 13.35±3.53. At the same time, the cell cycle initiation-related genes ras association domain family member 1 (RASSF1), cyclin dependent kinase 2 (CDK2), superoxide dismutase 2 (SOD2), which were promoted in expression by MYC, were down-regulated at hour 0 after PH, but the cell cycle initiation-related genes nestin (NES), RAD21 cohesin complex component (RAD21), CUE domain containing 2 (CUEDC2), which are inhibieted in expression by MYC, had no meaningful express changes at hour 0 after PH. On the other hand, the cell cycle initiation-related gene SOD2, which was promoted in expression by MYC, was up-regulated at hour 6 after PH, but the cell cycle initiation-related genes NES, RAD21, CUEDC2, which are inhibieted in expression by MYC, were down-regulated at hour 6 after PH. In contrary, at hour 72 after PH, the ratio value of MYC mRNA showed 2.36±0.20, miR-880-3p indicated 0.54±0.01, circRNA_09599 displayd 0.54±0.16. At the same time, the cell cycle termination-related gene hepatocyte growth factor (HGF), which is promoted in expression by MYC, was up-regulated 72 hours after PH, the cell cycle termination-related genes MET proto-oncogene receptor tyrosine kinase (MET) and cyclin dependent kinase inhibitor 1A (CDKN1A), which are inhibieted in expression by MYC, were down-regulated 72 hours after PH. Conclusion The correlation in expression and role of the miRNAs, which are inhibited by circRNAs, MYC, its mRNA is inhibited by miRNAs, and the cell cycle initiation-related and cell cycle termination-related genes, which are regulated by MYC, are helpful for the hepatocyte to be in cell cycle initiation state at hour 6 after PH and to be in cell cycle termination state at hour 72 after PH.
ABSTRACT
[ Abstract] Objective To explore the role pathway and pattern of the Kruppel-like factor 4 (KLF4) and its mRNA interaction with microRNA (miRNAs) and circular RNA (circRNAs) at 0 hour and the 120 th hour in the rat liver regeneration. Methods The rat 2 / 3 hepatectomy (partial hepatectomy, PH) model was prepared as described by Higgins, the hepatocytes were isolated according to the method of Smedsrod et al, the expression changes of mRNA, miRNA and circRNA together named as competing endogenous RNA (ceRNA) were detected by the large-scale quantitative detection technology, the interaction network of ceRNA was constructed by Cytoscape 3. 2 software, and their correlation in expression and role were analyzed by ceRNA comprehensive analysis. Results It was found that at the 0 hour and the 120th hour PH, the ratio value of KLF4 mRNA showed 1. 00±0. 16 and 3. 14±0. 27, miR-881-3p displays 18. 30±1. 44 and 0. 47±0. 02, circRNA_20298 indicated 0. 32±0. 10 and 4. 24±0. 22, circRNA_14826 showed 0. 42±0. 13 and 0. 61±0. 08. At the same time, the four kinds of cell apoptosis-related genes adrenoceptor beta 2 (ADRB2), dimethylarginine dimethylaminohydrolase 2 (DDAH2), annexin A5 (ANXA5), ect, which were promoted in expression by KLF4, were down-regulated at 0 hour after PH, but the cell apoptosis-related genes synuclein gamma (SNCG), glutathione-disulfide reductase (GSR), FYVE, RhoGEF and PH domain containing 4 (FGD4), ect, which were inhibited in expression by KLF4, were up-regulated at 0 hour after PH. On the other hand, the cell apoptosis-related genes ANXA5 and thymosin beta 10 (TMSB10), which are promoted in expression by KLF4, were up-regulated at the 120th hour after PH, but the cell apoptosis-related genes chloride intracellular channel 4 (CLIC4) and ataxin 3 (ATXN3), ect, which were inhibited in expression by KLF4, were down-regulated at the 120th hour after PH. Conclusion The correlation in expression and role of the miRNAs, which are inhibited by circRNAs, KLF4, its mRNA is inhibited by miRNAs, and the cell apoptosis-related genes, which are regulated by KLF4, are helpful for the hepatocyte to be in active state 0 hour after PH and to be in apoptotic state 120-hour after PH.